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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 30 June 2019
Main ID:  EUCTR2018-003753-13-FR
Date of registration: 13/12/2018
Prospective Registration: Yes
Primary sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Public title: INTOReTAK : INfliximab and TOcilizumab in Refractory/relapsing TAKayasu arteritis
Scientific title: Multicentre, randomized, prospective trial comparing the efficacy and safety of Infliximab to tocilizumab in refractory or relapsing Takayasu arteritis
Date of first enrolment: 19/03/2019
Target sample size: 50
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003753-13
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: no
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: no
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
France
Contacts
Name: Project Manager   
Address:  DRCI Hôpital Saint Louis, 1 Av. Claude Vellefaux 75010 Paris France
Telephone: 330144 84 17 98
Email: aurelie.guimfack@aphp.fr
Affiliation:  ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Name: Project Manager   
Address:  DRCI Hôpital Saint Louis, 1 Av. Claude Vellefaux 75010 Paris France
Telephone: 330144 84 17 98
Email: aurelie.guimfack@aphp.fr
Affiliation:  ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Key inclusion & exclusion criteria
Inclusion criteria:
? Diagnosis of Takayasu disease according to the international criteria of the American College of Rheumatology (ACR) (appendix 1)
o Age at disease onset < 40 years
o Claudication of extremities
o Decreased brachial artery pulse (one or both arteries)
o Blood pressure difference of >10mm Hg between the arms
o Bruit over subclavian arteries or aorta
? Active disease according to the international criteria of the National Institute of Health (NIH) (appendix 2)
New onset or worsening of at least two of the following four criteria
o Systemic features
o Elevated erythrocyte sedimentation rate
o Features of vascular ischemia or inflammation
o Typical angiographic features
? Refractory/relapsing disease
o Failure of disease to respond to daily corticosteroids therapy (1mg/kg/day for > 1month), i.e. disease still active
o Inability to taper corticosteroids below 10mg/day within 6 months
o Inability to discontinue corticosteroids after 1 year of treatment
o Relapse of disease after gradual decrease of corticosteroids therapy
? Patients with one immunosuppressive agent (methotrexate, azathioprine, mercaptopurine or mycophenolate mofetil)
? Age of 18 years or older
? Weight 40 – 120 kg
? Medical follow-up in a university or general hospital in France
? Social insurance
? Willing and able to provide written informed consent
? Willing and able to comply with treatment and follow-up procedures required by the study protocol
? For female subjects of child-bearing age, a negative serum pregnancy test
? For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject’s partner from becoming pregnant during the study. Adequate contraceptive measures include hormonal methods used for two or more cycles prior to Screening (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly, or condom used in conjunction with contraceptive foam or jelly), intrauterine methods (IUD), sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner), and abstinence.
? Chest X-ray results (postero-anterior and lateral) within 12 weeks prior to enrollment with no evidence of active tuberculosis, active infection, or malignancy
? Tuberculosis assessment:
o Active Tuberculosis infection treatment achieved
o Completion of at least 3 weeks treatment for Latent Tuberculosis infection
o Negative tuberculin skin test (TST) or interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test)
A potential subject with a positive TST or IGRA at inclusion is eligible if her/his chest X-ray does not show evidence suggestive of active tuberculosis infection and there are no clinical signs and symptoms of pulmonary and/or extra-pulmonary tuberculosis infection. These subjects with a latent tuberculosis infection who have not already received a prophylactic tuberculosis treatment must agree in advance to complete such a treatment course.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
? Active tuberculosis or untreated latent tuberculosis
? Evidence of active infection (includes chronic infection)
? Infection requiring treatment with antibiotics within 2 weeks prior to enrollment
? Infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen.
? Pregnancy or lactation
? Inability to comply with study guidelines
? Inability to provide informed consent
? Immunosuppressant type or dose modification within 30 days prior to enrollment
? Alcohol or drug abuse, that, in the investigator’s opinion, could prevent a subject from fulfilling the study requirements or that would increase the risk of study procedures
? Severe renal insufficiency (creatinine clairance <30mL/min/1,73m2)
? Hepatic dysfunction as shown by aspartate transaminase (AST) or alanine transaminase (ALT) levels >5-fold the upper limit of normal
? Heart failure = stage III / IV NYHA,
? History of any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin, or solid tumors treated with curative therapy and disease free for at least 5 years.
? History of multiple sclerosis and/or demyelinating disorder
? History of severe allergic or anaphylactic reactions to cyclophosphamide, interferon or infliximab and prednisone.
? History of immediate hypersensitivity reaction to iodinated and gadolinium-based contrast media
? Cytopenia: Hemoglobin < 8.5 g/dL, absolute neutrophil < 1.5 G/L, Platelet count < 80 G/L
? Any live (attenuated) vaccine fewer than 4 weeks before enrolment. Recombinant or killed virus vaccines fewer than 2 weeks before enrolment.
? Use of the following systemic treatments during the specified periods
a-Treatment with biologic therapy (infliximab, adalimumab, certolizumab pegol, golimumab, anakinra, tocilizumab, etanercept, abatacept, ixekizumab, secukinumab, ustekinumab, alemtuzumab) within 6 months prior to enrollment
b-Past treatment with rituximab within the past 12 months, or past treatment with rituximab more than 12 months ago where the B lymphocytes count has not returned to normal at time of enrollment
c-Treatment with any systemic alkylating agents within 6 months prior to enrollment (e.g., cyclophosphamide, chlorambucil)
?History of hypersensitivity to infliximab, other murine proteins, or to any of the excipients
?Hypersensitivity to Tocilizumab or to any of the excipients
? Lack of affiliation to a social security benefit plan (as a beneficiary or assignee)
? Presence of any of the following disease processes:
o Microscopic polyangiitis



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Patients with refractory or relapsing Takayasu Arteritis desease
Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]
Intervention(s)

Trade Name: RoActemra 20mg/ml
Product Name: Tocilizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Tocilizumab
CAS Number: 375823-41-9
Other descriptive name: TOCILIZUMAB
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 80-400

Product Name: Infliximab
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)
Main Objective: To obtain = 70% of patients with prednisone = 0.1mg/kg per day and inactive disease during 3 months at 6 months after randomization.
Proportion at 6 months after randomization of patients with prednisone = 0.1mg/kg per day and sustained inactive disease from M3 to M6.
Primary end point(s): Proportion at 6 months after randomization of patients with prednisone = 0.1mg/kg per day and sustained inactive disease from M3 to M6.
Secondary Objective: To compare, after randomization between the 2 arms.
Incidence of relapse between 3 and 6 months
Incidence of traitement failure at 3 months
Incidence of revascularization procedures (endovascular or surgical) required due to the disease
Cumulative dose of prednisone at 6 & 12 months
Incidence of adverse events at 6 & 12 months
Mean change in SF-36 quality-of-life values from randomization to 6 & 12 months
Proportion of new vascular lesions at 6 & 12 months
Incidence of relapse as defined by the NIH criteria between 3 and 6 months
Incidence of revascularization procedures (endovascular or surgical) from randomization to 6 months
Cumulative doses of prednisone in each arm at 6 & 12 months
Incidence of adverse events of grades III and IV at 6 & 12 months
Mean change in the quality of life questionnaire SF-36 from randomization to 6 & 12 months
Proportion of new vascular lesions at 6 & 12 months
Incidence of adverse event grade III or IV during 6 & 12 months
Timepoint(s) of evaluation of this end point: 6 months after randomization of patients
Secondary Outcome(s)
Secondary end point(s): Incidence of relapse as defined by the NIH criteria between 3 and 6 months.
Incidence of revascularization procedures (endovascular or surgical) from randomization to 6 months after randomization.
Cumulative doses of prednisone in each arm at 6 & 12 months after randomization.
Incidence of adverse events of grades III and IV at 6 & 12 months after randomization.
Mean change in the quality of life questionnaire SF-36 from randomization to 6 & 12 months after randomization.
Proportion of new vascular lesions at 6 & 12 months after randomization measured by angio-CT or MR angiography
Incidence of adverse event grade III or IV during 6 & 12 months after randomization.
Timepoint(s) of evaluation of this end point: 6 & 12 months after randomization
from randomization to 6 & 12 months after randomization.
Secondary ID(s)
P160909
Source(s) of Monetary Support
DGOS
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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